Nail infections are common conditions of the nail. Onychomycosis, a fungal infection of the nail bed, matrix, or nail plate, is the most common nail infection. The primary clinical features of onychomycosis are distal onycholysis (separation of the nail plate from the nail bed), subungual hyperkeratosis, and a dystrophic, discolored nail. Patients afflicted with onychomycosis are usually embarrassed by their nail disfigurement, but the infection is more than a cosmetic problem. It can sometimes limit mobility and indirectly decrease peripheral circulation, thereby worsening conditions such as venous stasis and diabetic ulcers. Fungal infections of the nail can also spread to other areas of the body and potentially to other persons. The fungal infection can be caused by dermatophytes (e.g., Trichophyton rubrum and T. mentagrophytes), but may also be due to infection by Candida species or nondermatophyte molds such as Aspergillus species, Scopulariosis brevicaulis, Fusarium species, and Scytalidium species.
Currently, oral antifungal agents are the mainstay of treatment for onychomycosis. For example, Sporonox®. capsules (itraconazole) (Janssen Pharmaceutica Products, L.P., Titusville, N.J. and Ortho Biotech Products, L.P., Raritan, N.J.), Lamisil® tablets (terbinafine hydrochloride) (Novartis Pharmaceuticals, East Hanover, N.J.), Diflucan® tablets and fluconazole (Pfizer, New York, N.Y.) are commonly prescribed antifungal agents. However, these oral antifungal products are associated with many minor systemic side effects such as headaches, stomach upset, skin rashes, and photosensitivity, as well as serious systemic side effects such as heart failure and liver failure. Although oral antifungal therapy is preferred, risk of the serious side effects often outweighs therapeutic benefit, and drug-drug interactions are a problem for many patients. The prolonged treatment regimen of one dose daily for at least three months, or once weekly for nine to twelve months also leads to poor patient compliance with oral antifungal therapy.
Topical therapy with antifungal agents is an alternative to oral therapy, and a topical solution, Penlac® nail lacquer (ciclopirox solution, 8%) (Dermik Laboratories, Berwyn, Pa.), is approved by the FDA for the topical treatment of mild to moderate onychomycosis. However, the topical mode of administration is seldom effective to treat more than mild nail unit infections because the active agent is unable to effectively penetrate the nail. Topical therapy accompanied by chemical or physical abrasion of the nails has also been largely unsuccessful. Topical antifungal therapy usually also involves daily application to the nails for several months, and thus, also poses a compliance problem. Topical nail treatment typically precludes the use of nail cosmetics/polish that otherwise would be used to camouflage the diseased and/or disfigured nail plate.
Psoriasis is estimated to affect approximately 2% of the population. As many as 50% of psoriasis patients may have nail involvement (psoriatic nail disease or nail psoriasis) with a lifetime incidence in psoriasis patients reaching 80-90%. Nail disease without cutaneous involvement is present in an estimated 5-10% of psoriasis patients. Common features of nail psoriasis include pitting (present in an estimated 68% of affected patients), onycholysis (in 67%), subungual hyperkeratosis (in 25%), oil drop signs (discoloration), crumbling of the nail plate, and splinter hemorrhage, the latter four of these being associated with nail bed involvement. In addition to the obvious cosmetic problem, many patients with nail psoriasis, especially when the fingernails are involved, suffer pain, loss of manual dexterity, and diminished sensation of touch. Onychomycosis may additionally be present with nail psoriasis.
Medications that have been used with varying degrees of success in treating nail psoriasis include corticosteroids (e.g. betamethasone dipropionate, clobetasol, triamcinolone acetonide), vitamin D analogs or derivatives (e.g. calcipitriol, calcipotriene, tacalcitol, calcitriol), retinoids (tazarotene, etretinate), biologicals (e.g. infliximab, adalimumab), antimetabolite drugs such as 5-fluorouracil, and immunosuppressants/calcineurin inhibitors such as cyclosporine and tacrolimus. Topical application of medications has limited use as the medication may not penetrate the nail plate to reach the affected area. Specifically for psoriasis involving the nail bed, where onycholysis and subungual hyperkeratosis are prominent, topically applied antipsoriatic agents have limited transungual penetration into the affected nail bed. Corticosteroid injections into the nail bed have been used with varying results.
Overall, treatment of diseases of the nail unit remains challenging and there remains a continuing need for the development of effective means for the treatment of diseases of the nail unit, particularly diseases that call for delivery of active ingredient to the nail unit for sustained periods of time. An additional need is for treatments that minimize pain.
The foregoing examples of the related art and limitations related therewith are intended to be illustrative and not exclusive. Other limitations of the related art will become apparent to those of skill in the art upon a reading of the specification and a study of the drawings.